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BloombergBusinessweek March 23, 2020patients,oncoronaviruspatientsaroundtheworld.Gilead
expectstoreportinitialresultsinApril.
Scientistssaytheycantamethiscoronavirus,butfora while
it willmovefasterthanthey’llbeableto.It maybea yearor
morebeforeanyspecifictreatmentforCovid-19is available.
Untilthenwe’llhavetocontainit withdistanceandsoapand
thedrugswealreadyhave.
Evenoncethere’sa treatment,it’sprobablethatCovid-19
willremainwithusforlongerthanwe’dlike.Completelywip-
ingoutsomethingthiswidespreadis exceedinglydifficult,Ho
is quicktosay.Onlyonesuchvirushasbeeneradicated:small-
pox.Thattookabout 20 years.O
n anearlyMarchmorning,beforeNewYorkCity
beganclosingdown,Hotooksometimetotalkabout
theworkunderwayathislab.Heworea suit,and
thoughheseemedperfectlycomfortable,he’dnormallybein
jeans.He’dbebusy,buthisphonewouldn’tbeconstantlyring-
ing.Hewouldn’tbemeetingwithuniversitytrustees,oradvis-
ingtheNBA,orconferringwiththeheadofChina’scenterfor
diseasecontrolandprevention,orappearingontheRachel
MaddowShow. He’dbeexpectinghisstafftohaveunpacked
theirmovingboxes.
Butthisisn’ta normaltimeforanyone,andespeciallynot
fora scientistsuchasHo.Hewasamongthefirsttochampion
a powerfulcombinationofdrugstoattackHIVandtopushfor
themtobeadministeredearlyinsteadofaftera patientdevel-
opedsymptoms.It wasanunconventionalapproachthatbecame
thestandardofcareandhelpsexplainwhyHIVis a chronicdis-
easebutnotnecessarilya deadlyone.It alsoexplainswhyHo
wasthefirstdoctortobenamedTimemagazine’sManofthe
Year,in1996,andfiveyearslaterwasawardedthePresidential
CitizensMedal.Theplaquehangsonthewallbehindhisdesk.
Hois 67yearsold,measuredandfocused,andcentraltoa
networkofformercolleaguesandstudentswho’veknownthat
a momentlikethiswascoming:a pandemicthatcouldbethe
biggestviralthreattohumanitysinceHIVemergedinthe1980s.
Hohasdevelopedanambitiousandexpeditedefforttocome
upwithcoronavirusdrugs.Theearlystagesofdrugdevelop-
menttypicallytakefromfiveto 10 years,buthethinksit’s
possibletohavethemostpromisingcompoundsreadyforani-
maltestinginonlyone.Hishopeis tocreatea singlepillthat
couldtreatthiscoronavirusandtheonesthatwillcomeafter.
“Surelytherewillbeanotherone,”hesays.“Thisis thethird
outbreakintwodecades.”SARSstartedinChinaandeventu-
allykilledalmost 800 people;MiddleEastrespiratorysyndrome
emergedin 2012 andhaskilledmorethan 850 insporadicout-
breakssincethen.
“We’rereadingstrangeliteratureaboutbatresearch,”Ho
says.“Batsaccountforone-fifthofthemammalsonthisplanet.
That’striviawedidn’tknow.Therearesomanyvirusesthat
resideinbats—SARSandEbolaandperhapsthiscoronavirus.”
Covid-19 isn’t the first, and it won’t be the last. Ho wants to pre-
pare for the next one now.
Hearing that was good enough for Jack Ma, the richest maninAsia.Andit wassufficientforZhiHong,chiefexecutive
officer of Brii Biosciences, to also put in $2 million. Hong had
been an infectious disease expert at GlaxoSmithKline Plc and
has known Ho for years. “David has put together a quick but
very reasonable program,” Hong says. If Ho’s lab comes up
with a drug, a big pharmaceutical company would have to
come in to test and produce it. There’s no formal agreement
yet about how that would happen. There was no time for law-
yers. “Right now we’re just investing in faith and trust in the
relationship and David’s reputation,” Hong says. “We just said,
‘Take the money.’ ”
The most straightforward of the lab’s projects aims to find
an antibody to block the virus from entering cells, either to pre-
vent infection or to treat it. The first step was getting hold of
specific white blood cells, called memory B cells, from patients
who have recovered from Covid-19. These cells, named because
they can remember a virus for decades, contain markers on
their surfaces that allow the body to rapidly generate many
antibodies to that virus. These antibodies help protect against
Covid-19 infection. In late January, Ho called on his connec-
tions in Hong Kong to take blood samples from two convales-
cent patients. His New York staff spent days getting permission
from the governments and arranging the shipping. The cells
were purified, placed in tiny vials, frozen in liquid nitrogen at
–150C, and sent to Ho’s lab by a specialized courier service.
They arrived intact in late February.
As soon as they received the cells, Ho’s lab went to work
sorting out the B cells, extracting RNA, making DNA for numer-
ous anti-coronavirus antibodies, and expressing those antibod-
ies on the surface of yeast cells. “Then we go fishing,” Ho says.
“And we come with bait.” The bait is the spike proteins that
protrude from the surface of the virus—or, in this instance, the
lab-created pseudo virus. The tighter an antibody binds to the
protein, the better. “We pull out many, compare activity, and
select the best,” he says. “We could then change parts of the
antibody to make it fit even tighter.”
The chances that this research, or similar research elsewhere,
will yield a treatment are relatively high. The strategy worked
forEbola.RegeneronPharmaceuticalsInc.,whichdeveloped
a successfulEbolaantibodytreatment,isalsoworkingona
coronavirus antibody “cocktail” and says human trials could
begin by early summer. But any such drug would have to be
injected, which would likely require it to be refrigerated and
administered by doctors—all of which would limit its use. It’s
not the ideal. But it’s what might be good enough as a start.H
o’s early HIV research focused on a crucial enzyme
called protease, which acts as a kind of molecular scis-
sors,cuttingupviralproteinstohelpthemreplicate.
OnekeysetofdrugshetestedonHIVpatientsinthe1990swere
proteaseinhibitors:Theyinterruptedthatstageofthevirallife
cycleinaninfectedpatient.He’shopingtoidentifypotential
coronavirus protease inhibitors, which would act in much the
same way. “Even if the protease is different, there are enough
similarities to apply our knowledge and the chemistry,” he says.